Is ABHD15 p.Ser327Arg (c.981C>G) pathogenic?

ABHD15 p.Ser327Arg (c.981C>G) is classified Uncertain significance in ABHD15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.016%, afr).

How common is ABHD15 p.Ser327Arg (c.981C>G) in the general population?

ABHD15 p.Ser327Arg (c.981C>G) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about ABHD15 p.Ser327Arg (c.981C>G)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

ABHD15 p.Ser327Arg

c.981C>G · VCV4636312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -4.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -5.1, phastCons 0.007
Regional constraint	o/e 0.99	unconstrained · MANE · 4,402 bp · p 0.8 · regional, not allelic
Overall
CADD	10.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/75,050 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000806% 13/1,613,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,254
Remaining individualsnot grpmax-eligible	0.0016%	62,504

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABHD15
Protein: p.Ser327Arg
Coding: c.981C>G
MANE Select: NM_198147
Type: single nucleotide variant
Location: chr17:29562987 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.70

Full ABHD15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD15 p.Ala16Pro Uncertain significance ★ ⚠ same type
ABHD15 p.Ala228Val Uncertain significance ★ ⚠ same type
ABHD15 p.Ala229Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala233Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala260Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala291Thr Uncertain significance ★ ⚠ same type
ABHD15 p.Ala358Pro Uncertain significance ★ ⚠ same type
ABHD15 p.Ala444Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abhd15-p-ser327arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown